Dynamic Microvalve Protection Device

ABSTRACT

An endovascular system includes inner and outer catheters, a handle system operably coupled one end of the catheters, and a microvalve coupled to the other end of the catheters. The microvalve is constrained in a radially-collapsed closed configuration for advancement within a vessel to a treatment site. The handle system is operable to displace the inner and outer catheters portions relative to each other to move the microvalve between closed and open configurations. An indicator is provided to visually indicate the extent by which the microvalve is opened within the vessel.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 15/804,839, filedNov. 6, 2017, which is a continuation of U.S. Ser. No. 14/806,596, filedJul. 22, 2015, and now issued as U.S. Pat. No. 9,808,332, which is acontinuation of U.S. Ser. No. 13/306,105, filed Nov. 29, 2011, and nowissued as U.S. Pat. No. 9,539,081, which is a continuation-in-part ofU.S. Ser. No. 12/957,533, filed Dec. 1, 2010, and now issued as U.S.Pat. No. 8,696,698,

which claims the benefit of U.S. Ser. No. 61/382,290, filed Sep. 13,2010, and

which is also a continuation-in-part of U.S. Ser. No. 12/829,565, filedJul. 2, 2010, and now issued as U.S. Pat. No. 8,500,775, which claimspriority from U.S. Ser. No. 61/266,068, filed Dec. 2, 2009, all of whichare hereby incorporated by reference herein in their entireties.

BACKGROUND OF THE INVENTION 1. Field of Invention

The present invention relates generally to a medical embolizingtreatment method that utilizes a protection device to increasepenetration of a treatment agent into targeted blood vessels and reducereflux of the treatment agent into non-targeted vessels.

2. State of the Art

Embolization, chemo-embolization, and radio-embolization therapy areoften clinically used to treat a range of diseases, such ashypervascular liver tumors, uterine fibroids, secondary cancermetastasis in the liver, pre-operative treatment of hypervascularmenangiomas in the brain and bronchial artery embolization forhemoptysis. An embolizing agent may be embodied in different forms, suchas beads, liquid, foam, or glue placed into an arterial vasculature. Thebeads may be uncoated or coated. Where the beads are coated, the coatingmay be a chemotherapy agent, a radiation agent or other therapeuticagent. When it is desirable to embolize a small blood vessel, small beadsizes (e.g., 10 μm-100 μm) are utilized. When a larger vessel is to beembolized, a larger bead size (e.g., 100 μm-900 μm) is typically chosen.

While embolizing agent therapies which are considered minimally orlimited invasive have often provided good results, they have a smallincidence of non-targeted embolization which can lead to adverse eventsand morbidity. An infusion microcatheter allows bi-directional flow.That is, the use of a microcatheter to infuse an embolic agent allowsblood and the infused embolic agent to move forward in addition toallowing blood and the embolic agent to be pushed backward (reflux).Reflux of a therapeutic agent causes non-target damage to surroundinghealthy organs. In interventional oncology embolization procedures, thegoal is to bombard a cancer tumor with either radiation or chemotherapy.It is important to maintain forward flow throughout the entire vasculartree in the target organ in order to deliver therapies into the distalvasculature, where the therapy can be most effective. This issue isamplified in hypovascular tumors or in patients who have undergonechemotherapy, where slow flow limits the dose of therapeutic agentdelivered and reflux of agents to non-target tissue can happen wellbefore the physician has delivered the desired dose.

The pressure in a vessel at multiple locations in the vascular treechanges during an embolic infusion procedure. Initially, the pressure ishigh proximally, and decreases over the length of the vessel. Forwardflow of therapy occurs when there is a pressure drop. If there is nopressure drop over a length of vessel, therapy does not flow downstream.If there is a higher pressure at one location, such as at the orifice ofa catheter, the embolic therapy flows in a direction toward lowerpressure. If the pressure generated at the orifice of a catheter islarger than the pressure in the vessel proximal to the catheter orifice,some portion of the infused embolic therapy travels up stream (reflux)into non-target vessels and non-target organs. This phenomenon canhappen even in vessels with strong forward flow if the infusion pressure(pressure at the orifice of the catheter) is sufficiently high.

During an embolization procedure, the embolic agents clog distal vesselsand block drainage of fluid into the capillary system. This leads to anincrease in the pressure in the distal vasculature. With the increasedpressure, there is a decrease in the pressure gradient and thereforeflow slows or stops in the distal vasculature. Later in the embolizationprocedure, larger vessels become embolized and the pressure increasesproximally until there is a system that effectively has constantpressure throughout the system. The effect is slow flow even in thelarger vessels, and distally the embolic agent no longer advance intothe target (tumor).

In current clinical practice, the physician attempts to infuse embolicswith pressure that does not cause reflux. In doing this, the physicianslows the infusion rate (and infusion pressure) or stops the infusioncompletely. The clinical impact of current infusion catheters andtechniques is two fold: low doses of the therapeutic embolic isdelivered and there is poor distal penetration into the target vessels.

Additionally, reflux can be a time-sensitive phenomenon. Sometimes,reflux occurs as a response to an injection of the embolic agent, wherethe reflux occurs rapidly (e.g., in the time-scale of milliseconds) in amanner which is too fast for a human operator to respond. Also, refluxcan happen momentarily, followed by a temporary resumption of forwardflow in the blood vessel, only to be followed by additional reflux.

FIG. 1 shows a conventional (prior art) embolization treatment in thehepatic artery 106. Catheter 101 delivers embolization agents (beads)102 in a hepatic artery 106, with a goal of embolizing a target organ103. It is important that the forward flow (direction arrow 107) ofblood is maintained during an infusion of embolization agents 102because the forward flow is used to carry embolization agents 102 deepinto the vascular bed of target organ 103.

Embolization agents 102 are continuously injected until reflux ofcontrast agent is visualized in the distal area of the hepatic artery.Generally, since embolization agents 102 can rarely be visualizeddirectly, a contrast agent may be added to embolization agents 102. Theaddition of the contrast agent allows for a visualization of the refluxof the contrast agent (shown by arrow 108), which is indicative of thereflux of embolization agents 102. The reflux may, undesirably, causeembolization agents 102 to be delivered into a collateral artery 105,which is proximal to the tip of catheter 101. The presence ofembolization agents 102 in collateral artery 105 leads to non-targetembolization in a non-target organ 104, which may be the other lobe ofthe liver, the stomach, small intestine, pancreas, gall bladder, orother organ.

Non-targeted delivery of the embolic agent may have significant unwantedeffects on the human body. For example, in liver treatment, non-targeteddelivery of the embolic agent may have undesirable impacts on otherorgans including the stomach and small intestine. In uterine fibroidtreatment, the non-targeted delivery of the embolic agent may embolizeone or both ovaries leading to loss of menstrual cycle, subtle ovariandamage that may reduce fertility, early onset of menopause and in somecases substantial damage to the ovaries. Other unintended adverse eventsinclude unilateral deep buttock pain, buttock necrosis, and uterinenecrosis.

Often, interventional radiologists try to reduce the amount and impactof reflux by slowly releasing the embolizing agent and/or by deliveringa reduced dosage. The added time, complexity, increased x-ray dose tothe patient and physician (longer monitoring of the patient) andpotential for reduced efficacy make the slow delivery of embolizationagents suboptimal. Also, reducing the dosage often leads to the need formultiple follow-up treatments. Even when the physician tries to reducethe amount of reflux, the local flow conditions at the tip of thecatheter change too fast to be controlled by the physician, andtherefore rapid momentary reflux conditions can happen throughoutinfusion.

SUMMARY OF THE INVENTION

According to one aspect of the invention, a deployable apparatus isprovided that is useful in an embolization procedure and which enablessubstantially unrestricted forward flow of blood in a vessel and reducesor stops reflux (regurgitation or backward flow) of embolization agentswhich are introduced into the blood.

In some embodiments, the deployable apparatus includes a deliverycatheter having a valve fixedly coupled to the distal end thereof. Anouter catheter is provided which extends over the valve duringintroduction to maintain the valve in a collapsed cylindricalconfiguration until the valve is advanced through the patient to thedesired vascular destination. Once at the destination, the outercatheter is retracted from over the valve to permit expansion of thevalve into an open state, as discussed below.

In other embodiments, the deployable apparatus includes a deliverycatheter and a valve introducer which delivers a valve to a valve seatat the distal end of the delivery catheter during the embolizationprocedure. No outer catheter is required. A valve introducer maintainsthe distal end of the valve in a closed configuration, and a push wireis abutted against the proximal end of the valve and used to push thevalve out of the valve introducer and through the delivery catheter. Thevalve is advanced by the push wire to the valve seat located at thedistal end of a delivery catheter. Once the valve seat captures aproximal portion of the valve to lock the valve at the distal end of thedelivery catheter, the push wire is then withdrawn from the deliverycatheter to provide an apparatus with enhanced fluid flow through thedelivery catheter. In certain embodiments a pull member is coupled tothe valve to release the lock between the valve and valve seat andpermit retraction of the valve into the delivery catheter after theembolic agent has been dispensed.

The deployable valve includes a plurality of filaments which cross overeach other (i.e., are braided) and which have a spring bias to assume apreferred crossing angle relative to each other. In a first state, thevalve is preferably kept in a cylindrical arrangement with a diametersubstantially equal to the diameter of the delivery catheter. In asecond state, the valve is free to open due to the spring bias in thefilaments. In the second state, with the proximal end of the valveattached to the delivery catheter, in the bloodstream, if the blood isnot flowing distally past the valve, the valve assumes a substantiallyfrustoconical shape. The distal end of the valve is intended to makecontact with the walls of the vessel in which it is deployed when bloodis not flowing distally past the valve.

In some embodiments, the valve, while enabling substantiallyunrestricted forward flow in a vessel and reducing or stopping reflux ofembolization agents, allows the reflux of blood or contrast agent. Inother embodiments, the valve, while enabling substantially unrestrictedforward flow in a vessel and reducing or stopping reflux of embolizationagents, also reduces or stops backward flow of blood.

According to one aspect of the invention, the valve has a radial forceof expansion when in the undeployed state of less than 40 mN.

According to another aspect of the invention, the valve has a timeconstant of expansion from the cylindrical arrangement to the fully-openposition when in a static fluid having a viscosity of approximately 3.2cP of between 1.0 and 0.01 seconds, and more preferably between 0.50 and0.05 seconds.

According to a further aspect of the invention, the valve has a Young'smodulus of elasticity that is greater than 100 MPa.

According to yet another aspect of the invention, the preferred crossingangle of the valve filaments is approximately 130 degrees.

According to even another aspect of the invention, the filaments of thevalve are selected to be of a desired number and diameter such that inan open position, they are capable of trapping embolization agents. Byway of example only, the filaments of the valve are selected so that inan open position they present a pore size of 500 μm and are thus capableof preventing reflux of embolizing agent such as beads having a sizelarger than 500 μm. As another example, the filaments of the valve areselected so that in an open position they present a pore size of 250 μmand are thus capable of preventing reflux of embolizing agent having asize larger than 250 μm.

In one embodiment, the valve filaments are coated with a filter which isformed and attached to the filaments according to any desired manner,such as by spraying, spinning, electrospinning, bonding with anadhesive, thermally fusing, melt bonding, or other method. The filter ispreferably arranged to have a desired pore size, although it will beappreciated that the pore size may be non-uniform depending upon thetechnique in which the filter is formed and attached. By way of example,the pore size of the filter may be approximately 40 μm such thatembolizing agents having a characteristic size of more than 40 μm areprevented from refluxing past the valve. By way of another example, thepore size of the filter may be approximately 20 μm such that embolizingagents having a characteristic size of more than 20 μm are preventedfrom refluxing past the valve. In both cases, blood cells (which have acharacteristic size smaller than 20 μm), and contrast agent which has amolecular size smaller than 20 μm will pass through the filter andvalve.

According to an additional aspect of the invention, when in a fully-openposition where the filaments assume the preferred crossing angle, thevalve is adapted to have a distal diameter which is at least twice thediameter of the delivery catheter, and preferably at least five timesthe diameter of the delivery catheter.

In one embodiment, the filaments are all formed from a polymer. Inanother embodiment, one or more of the filaments is formed fromstainless steel, platinum or platinum-iridium.

In an embodiment where one or more filaments are formed from a polymer,the filaments that are formed from the polymer are preferably melted attheir proximal end into the delivery catheter.

The valve may be deployed in any of several manners. Thus, by way ofexample only, in appropriate embodiments, an outer catheter or sleeveextending over the delivery catheter may be used to keep the valve in anundeployed state, and the outer catheter or sleeve may be pulledbackward relative to the delivery catheter in order to deploy the valve.Where an outer catheter or sleeve is utilized, the valve may be capturedand returned to its undeployed position by moving the delivery catheterproximally relative to the outer catheter or sleeves.

As another example, the distal end of the valve may be provided withloops which are adapted to engage a guidewire which extends through anddistal the distal end of the delivery catheter and through the distalloops of the valve. When the guidewire is withdrawn proximally, thevalve deploys.

As another example, a knitted sleeve with a control thread can beprovided to cover the valve. The control thread, when pulled, causes theknitted sleeve to unravel, thereby releasing the valve.

As yet another example, when no outer catheter is provided, the valvemay be deployed by advancement through the delivery catheter andengagement between a valve seat at the distal end of the deliverycatheter and corresponding mating structure at the proximal end of thevalve. When the valve is engaged in the valve seat, the valve filamentsextend distally of the delivery catheter and without further constrainton dynamic operation of the valve.

In addition, the valve may be retracted in any of several manners. Wherean outer catheter is provided, the outer catheter and delivery catheterare movable relative to each other to cause the outer catheter tocollapse the valve. In some embodiment where no outer catheter isprovided, the valve may be released from the distal end of the deliverycatheter and withdrawn, either so that it is drawn completely into thedelivery catheter or completely withdrawn from the proximal end of thedelivery catheter. One or more pull wires, including a braided constructmay be attached to the valve to aid in such withdrawal of the valve. Itis also appreciated that the valve may be withdrawn from the patient ina deployed state, if necessary.

In operation, the deployable apparatus operates as a one-way infusionsystem which allows forward flow of blood and infusate, but dynamicallyblocks reverse flow of embolics and most of the fluid that would flowbackward during a reflux condition. During infusion in high downstreamflow conditions, the valve of the deployable apparatus collapses andallows flow into downstream vascular branches. Any time the pressure inthe orifice of the catheter (inside the expandable valve) increaseshigher than the pressure in the blood vessel, the expandable valveimmediately opens and seals to the blood vessel wall, thus blockingupstream reflux of embolics. It is important to note that pressure iscommunicated throughout the vasculature at the speed of sound in blood(1540 m/s). Since the expandable valve responds to pressure changes, itreacts far faster than the flow rates of embolics in the blood (0.1m/s).

Thus, the expandable valve provides a mechanism for the physician toincrease pressure at the distal end of the catheter without riskingreflux. This allows the physician to drive greater distal penetration ofembolics than would be possible with a standard catheter. The apparatusmay be used to either infuse a greater amount of therapy, enhance distalpenetration of the therapy, or both. The device may also be used toinfuse a small bolus of therapy, and then a larger infusion of saline tocreate greater distal penetration of the relatively small dose oftherapy.

The design of the expandable valve filter may also be such that proteinsin the blood almost immediately fill the pores of the filter valve oncethe valve is deployed into the vessel. The coatings provide a safetyfeature of the valve, such that while the pores can be filled with theblood proteins at pressures at or greater than the safe blood vesselpressures. However, once the pressure in the vessel exceeds a thresholdpressure the coating facilitates release of the proteins from at thepores such that the pores are opened to thereby reduce intravesselpressure to a safe level. With the pores opened, blood can regurgitatethrough the pores of the filter valve, but the embolic agent continuesto be contained at the high pressure side of the filter valve, as theembolic agent is too large to pass through the pores.

BRIEF DESCRIPTION OF DRAWINGS

Prior art FIG. 1 shows a conventional embolizing catheter in a hepaticartery with embolizing agent refluxing into a non-targeted organ.

FIGS. 2A-2C are schematic diagrams of a first exemplary embodiment of anapparatus of the invention respectively in an undeployed state, adeployed partially open state with blood passing in the distaldirection, and a deployed fully open state where the blood flow isstatic.

FIGS. 3A and 3B are schematic diagrams of an exemplary embodiment of avalve having a braid component that is covered by a filter component inrespectively an undeployed state and a deployed state.

FIGS. 4A-4C are schematic diagrams of the exemplary embodiment of avalve of FIGS. 3A and 3B covered by a weft knit respectively in anundeployed state, a partially deployed state, and a more fully deployedstate.

FIGS. 5A-5B are schematic diagrams showing an exemplary embodiment of avalve that can be deployed by movement of a guidewire.

FIGS. 6A-6D show two exemplary methods of attaching the mesh componentof the valve to a catheter.

FIGS. 7A-7B show an exemplary embodiment of a valve composed of a singleshape memory filament and a filter.

FIGS. 8A-8D show an embodiment of exemplary structure and method forattaching a valve to the delivery catheter, with FIGS. 8B and 8D beingschematic cross-sections across line 8B-8B in FIG. 8A and line 8D-8D inFIG. 8C, respectively.

FIG. 8E is a schematic view of an introducer surrounding a valve and apush wire for introduction into the infusion port of a delivery catheterin accord with the embodiment shown in FIGS. 8A-8D.

FIGS. 9A-9D show another embodiment of exemplary structure and methodfor attaching a valve to the delivery catheter, with FIGS. 9B and 9Dbeing cross-sections across line 9B-9B in FIG. 9A and line 9D-9D in FIG.9C, respectively.

FIGS. 10A-13B show additional exemplary structures and methods forattaching a valve to the delivery catheter, with the ‘A’ and ‘B’ figurescorresponding to the valve being located in pre-seated position and apost-seated position, respectively, relative to a valve seat of thedelivery catheter.

FIGS. 14A-17B show embodiments with exemplary structure for releasingthe valve from the delivery catheter so that the valve may be withdrawninto the delivery catheter, with the ‘A’ and ‘B’ figures correspondingto longitudinal section and cross-section views, respectively.

FIGS. 18A and 18B show another embodiment of exemplary structure andmethod for attaching a valve to the delivery catheter.

FIG. 19 is a schematic view of the distal end of another embodiment ofan apparatus for delivering a valve at the distal end of a deliverycatheter.

FIG. 20 is a schematic view of the valve of FIG. 19.

FIGS. 21A-21C are distal end views of respective embodiments employingdifferent valve structure for the valve of FIG. 20.

FIGS. 22-23 illustrate the apparatus of FIG. 19 in deployedconfigurations.

FIGS. 24-26 are schematic views of another apparatus for deployment of asleeve valve, with FIG. 24 showing the valve in a housed configurationand FIGS. 25 and 26 showing the valve in two different deployedconfigurations.

FIGS. 27-29 are schematic views of an apparatus for deployment of avalve that uses a balloon, with FIG. 27 showing the valve in a closedconfiguration and FIGS. 28 and 29 showing the valve in two differentdeployed configurations.

FIGS. 30-32 are schematic view of another apparatus for deployment of afilter that uses a balloon.

FIG. 33 is a schematic view of another apparatus for deployment of avalve.

FIGS. 34-36 are schematic views of another apparatus for deployment of avalve, with FIGS. 34 showing the valve in a housed configuration, FIGS.35 showing the valve deployed, and FIG. 36 showing the valve in use.

FIGS. 37-40 are schematic views of another embodiment of an apparatusfor deployment of a valve, with FIG. 37 showing a initial closedconfiguration, FIGS. 38 and 39 illustrating deployed configurations, andFIG. 40 illustrated a re-assumed closed configuration.

FIGS. 41-43 illustrate several flush valves usable in conjunction withany of the other embodiments of the invention.

FIGS. 44-47 are schematic illustrations of another embodiment of anapparatus for deployment of valve.

FIGS. 48-51 are schematic illustrations of another embodiment of anapparatus for deployment of valve.

FIG. 52 is a schematic diagram of a prior art therapy infusion catheterinfusing an embolic agent into a vessel.

FIG. 53 is a schematic diagram of a therapy infusion apparatus accordingto the invention infusing an embolic agent into a vessel.

FIGS. 54-55 are photographs showing the penetration of an embolic agent(by visualization of a contrast agent) infused under standard prior artcatheterization techniques, with FIG. 55 being an enlargement of thearea highlighted in FIG. 54.

FIGS. 56-57 are photographs showing the penetration of an embolic agent(by visualization of a contrast agent) infused under the systems andtechniques of the invention, with FIG. 57 being an enlargement of thearea highlighted in FIG. 56.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A first exemplary embodiment of the invention is seen in FIGS. 2A-2C. Itis noted that FIGS. 2A-2C are not shown to relative size but rather areshown for purposes of explanation. In FIGS. 2A-2C a delivery catheter201 having a proximal end (not shown) and a distal end 205 is shownpositioned within an artery 204. The delivery catheter 201 is adaptedfor delivery of an embolizing agent from outside the body of the patient(not shown) to a target vessel (artery or vein) in the patient. Attachedto the distal end 205 of the catheter 201 is an exemplary embodiment ofa valve 203 shown having multiple filaments 203 a, 203 b, 203 c, . . .which are preferably braided and can move relative to each other. Asdiscussed hereinafter, the filaments are spring biased (i.e., they have“shape memory”) to assume a desired crossing angle relative to eachother so that the valve can assume a substantially frustoconical shape(it being noted that for purposes herein the term “substantiallyfrustoconical” should be understood to include not only a truncatedcone, but a truncated hyperboloid, a truncated paraboloid, and any othershape which starts from a circular proximal end and diverges therefrom).Around the catheter 201 is an outer catheter or sleeve 202 which ismovable over the delivery catheter 201 and valve 203. If desired, theouter catheter or sleeve 202 can extend the entire length of thedelivery catheter. Where the outer catheter or sleeve 202 extends alongthe entire length of the delivery catheter, it has a proximal end (notshown) which extends proximally and which can be controlled by apractitioner from outside the body of the patient. Alternatively, theouter catheter or sleeve 202 extends only over the distal end of thedelivery catheter 201 and valve 203, but is controlled by a controlelement which extends proximally and which can be controlled by apractitioner from outside the body of the patient.

As seen in FIG. 2A, when the outer catheter or sleeve 202 extends overthe valve 203, the multiple filaments are forced into a cylindricalshape. Thus, FIG. 2A shows the braid valve in an undeployed cylindricalstate, with the braid filaments 203 a, 203 b, 203 c . . . attached to adistal end of a catheter 205 and covered by the sleeve 202. Catheter 201is positioned within an artery 204 that has forward blood flow in thedirection of arrows 220. Such a condition occurs when the pressureupstream is greater than the pressure downstream. As seen in FIG. 2B,upon retraction of the sleeve 202 in the direction of arrow 210, thenon-constrained portion of the valve 203 is freed to expand radially(and retract longitudinally) in accord with its bias towards its shapememory position. Given the same pressure conditions, the valve does notopen more completely; i.e., it does not expand across the vessel wall.More particularly, at pressure greater than 10 mmHg causing the bloodflow indicated by arrows 220 and with no countervailing pressure, thevalve is prevented from opening more completely. As a result, the valve203 is maintained in a condition where it permits downstream blood flowand is not sufficiently open to block blood flow in the distaldownstream or proximal upstream ‘reflux’ directions.

FIG. 2C shows the valve 203 where there is blood pressure on theproximal side of the valve, but such pressure is lower than acountervailing pressure within the valve; i.e., such as during deliveryof embolic agents through catheter 201 and past the valve 203. In fact,such pressure may be significantly higher than the blood pressure. Inthe fully deployed arrangement of FIG. 2C, the braid valve acts as afilter to stop embolic agents from flowing proximal the valve. However,as discussed, depending upon the pore size of the braid valve 203, bloodand contrast agent may be permitted to flow backward through the valveand around the catheter 201 while preventing backflow of embolic agents.

It should be appreciated by those skilled in the art that the catheter201 can be any catheter known in the art. Typically, the catheter willbe between two and eight feet long, have an outer diameter of between0.67 mm and 3 mm (corresponding to catheter sizes 2 French to 9 French),and will be made from a liner made of fluorinated polymer such aspolytetrafluoroethylene (PTFE) or fluorinated ethylene propylene (FEP),a braid made of metal such as stainless steel or titanium, or a polymersuch as polyethylene terephthalate (PET) or liquid crystal polymer, andan outer coating made of a polyether block amide thermoplasticelastomeric resin such as PEBAX®, polyurethane, polyamide, copolymers ofpolyamide, polyester, copolymers of polyester, fluorinated polymers,such as PTFE, FEP, polyimides, polycarbonate or any other suitablematerial, or any other standard or specialty material used in makingcatheters used in the bloodstream. Sleeve or outer catheter 202 iscomprised of a material capable of holding valve braid 203 in acylindrical configuration and capable of sliding over the valve braid203 and the catheter 201. Sleeve or outer catheter 202 can be comprisedof polyurethane, polyamide, copolymers of polyamide, polyester,copolymers of polyester, fluorinated polymers, such as PTFE, FEP,polyimides, polycarbonate or any other suitable material. The sleeve orouter catheter may also contain a braid composed of metal such asstainless steel or titanium, or a polymer such as PET or liquid crystalpolymer, or any other suitable material. The wall thickness of sleeve orouter catheter 202 is preferably in the range of 0.05 mm to 0.25 mm witha more preferred thickness of 0.1 mm-0.15 mm.

The valve 203 is composed of one, two, or more metal (e.g., stainlesssteel or Nitinol) or polymer filaments, which form a substantiallyfrustoconical shape when not subject to outside forces. Where polymericfilaments are utilized, the filaments may be composed of PET,polyethylene-napthalate (PEN), liquid crystal polymer, fluorinatedpolymers, nylon, polyamide or any other suitable polymer. If desired,when polymeric filaments are utilized, one or more metal filaments maybe utilized in conjunction with the polymeric filaments. According toone aspect of the invention, where a metal filament is utilized, it maybe of radio-opaque material such that it may be tracked in the body. Thevalve is capable of expanding in diameter while reducing in length, andreducing in diameter while expanding in length. The valve is preferablycomposed of shape memory material that is formed and set in a largediameter orientation. As previously mentioned, the valve is preferablyheld in a small diameter orientation until it is released, and whenreleased by removing the sleeve or other restricting component 202, thedistal end of the valve expands to a larger diameter. Where the valve iscomprised of multiple filaments, it is preferred that the filaments notbe bonded to each other along their lengths or at their distal ends soto enable the valve to rapidly automatically open and close in responseto dynamic flow conditions.

In the preferred embodiment, the valve is constrained only at itsproximal end where it is coupled to the catheter body, while theremainder of the valve can either be constrained (retracted state) by asleeve or catheter, or partially unconstrained (partially deployedstate) or completely unconstrained (completely deployed state). When inthe partially or completely unconstrained conditions, depending upon theflow conditions in the vessel, the valve may either reach the walls ofthe vessel or it may not.

As previously mentioned, the valve diameter should automatically changein response to local pressure conditions so as to permit forward flowwhen the pressure proximal of the valve is higher than the pressurewithin and distal of the valve, but capture embolic agents during briefor prolonged periods of when the pressure within and distal of the valveis higher than proximal of the valve. For simplicity, the valve can beconsidered to exist in two conditions. In a “closed” condition, thevalve is not sealed against the vessel wall and blood may flow around inat least a proximal to distal direction. In an “open” condition, thevalve expands against the vessel wall and blood must pass through thevalve if it is to flow past the valve within the vessel in eitherdirection; in the “open” condition embolic agent is prevented frompassing downsteam (or in a distal to proximal direction) of the valve.

Three parameters help define the performance and novel nature of thevalve: the radial (outward) force of the valve, the time constant overwhich the valve changes condition from closed to open, and the pore sizeof the valve.

In a preferred embodiment, the valve expands fully to the vessel wall(i.e., reaches an open condition) when the pressure at the orifice ofthe catheter and within the valve is greater than the blood pressure(FIG. 2C), and remains in a closed condition when blood is flowingdistally with pressure greater than the pressure within and distal ofthe valve (FIG. 2B). In addition, when the radial force of expansion onthe valve (i.e., the expansion force of the valve itself in addition tothe force of pressure in the distal vessel over the distal surface areaof the valve) is greater than the radial force of compression on thevalve (i.e., force of pressure in the proximal vessel over the proximalsurface area of the valve), the valve fully expands to the configurationshown in FIG. 2C so that the valve assumes the open configuration. Thus,as seen, according to one aspect of the invention, the radial force ofexpansion of the valve is chosen to be low (as described in more detailbelow) so that normal blood flow in the downstream distal direction willprevent the valve from reaching the open condition. This low expansionforce is different than the expansion forces of prior art stents, stentgrafts, distal protection filters and other vascular devices, which havesignificantly higher radial forces of expansion.

The radial force of expansion of a braid is described by Jedwab andClerc (Journal of Applied Biomaterials, Vol. 4, 77-85, 1993) and laterupdated by DeBeule (DeBeule et al., Computer Methods in Biomechanics andBiomedical Engineering, 2005) as:

$F = {2{n\left\lbrack {{\frac{{GI}_{p}}{K_{3}}\left( {\frac{2\mspace{14mu} \sin \mspace{14mu} \beta}{K_{3}} - K_{1}} \right)} - {\frac{{EI}\mspace{14mu} \tan \mspace{14mu} \beta}{K_{3}}\left( {\frac{2\mspace{14mu} \cos \mspace{14mu} \beta}{K_{3}} - K_{2}} \right)}} \right\rbrack}}$

where K₁, K₂, K₃ are constants given by:

$K_{1} = {{\frac{\sin \mspace{14mu} 2\mspace{14mu} \beta_{0}}{D_{0}}\mspace{14mu} K_{2}} = {{\frac{2\mspace{14mu} \cos^{2}\mspace{14mu} \beta_{0}}{D_{0}}\mspace{14mu} K_{3}} = \frac{D_{0}}{\cos \mspace{14mu} \beta_{0}}}}$

and I and I_(p) are the surface and polar moments of inertia of thebraid filaments, E is the Young's modulus of elasticity of the filament,and G is the shear modulus of the filament. These material propertiesalong with the initial braid angle (β₀), final braid angle (β), stentdiameter (D₀), and number of filaments (n) impact the radial force ofthe braided valve.

In one embodiment, with a valve arrangement as shown in FIGS. 2A-2C, thevalve 203 is composed of twenty-four polyethylene terephthalate (PET)filaments 203 a, 203 b, . . . , each having a diameter of 0.1 mm andpre-formed to an 8 mm diameter mandrel and a braid angle of 130° (i.e.,the filaments are spring-biased or have a shape memory to assume anangle of 130° relative to each other when the valve assumes a fullydeployed state and opens in a frustoconical configuration). Thefilaments preferably have a Young's modulus greater than 200 MPa, andthe valve preferably has a radial force of less than 40 mN in the fullydeployed position (i.e., where the filaments assume their shape memory).More preferably, the valve has a radial force in the fully deployedposition of less than 20 mN, and even more preferably the valve has aradial force of approximately 10 mN (where the term “approximately” asused herein is defined to mean ±20%) in the deployed position. Where thevalve includes a filter as well as the braided filaments (as will bediscussed hereinafter with respect to FIGS. 3A and 3B), the braidcomponent preferably has a radial force of less than 20 mN in the fullydeployed position, and more preferably a radial force of less than 10mN, and even more preferably a radial force of approximately 5 mN. Thiscompares to prior art embolic capture devices such as the ANGIOGUARD® (atrademark of Cordis Corporation), and prior art Nitinol stents andstent-grafts which typically have radial forces of between 40 mN and 100mN in their fully deployed positions.

According to one aspect of the invention, the valve opens and closessufficiently quickly to achieve high capture efficiency of embolicagents in the presence of rapidly changing pressure conditions. Moreparticularly, any time the pressure at the distal opening of thecatheter (inside the expandable valve) increases higher than thepressure in the blood vessel, the expandable valve substantiallyimmediately opens and seals to the blood vessel wall, thus blockingrefluxing embolics. It is important to note that pressure iscommunicated throughout the vasculature at the speed of sound in blood(1540 m/s) and that the valve opens and closes in in response topressure changes within the blood vessel. Since the expandable valveresponds to pressure changes, it reacts far faster than the flow ratesof embolics in the blood (0.1 m/s) thereby preventing reflux of anyembolics.

In one embodiment, when subject to the infusion pressure at the catheterdistal end, the valve moves from a fully closed (undeployed) position toa fully open position in a static fluid (e.g., glycerin) having aviscosity approximately equal to the viscosity of blood (i.e.,approximately 3.2 cP) in 0.067 second. For purposes herein, the time ittakes to move from the fully closed position to the fully open positionin a static fluid is called the “time constant”. According to anotheraspect of the invention, the valve is arranged such that the timeconstant of the valve in a fluid having the viscosity of blood isbetween 0.01 seconds and 1.00 seconds. More preferably, the valve isarranged such that the time constant of the valve in a fluid having theviscosity of blood is between 0.05 and 0.50 seconds. The time constantof the valve may be adjusted by changing one or more of the parametersdescribed above (e.g., the number of filaments, the modulus ofelasticity of the filaments, the diameter of the filaments, etc.).

As will be appreciated by those skilled in the art, the braid geometryand material properties are intimately related to the radial force andtime constant of the valve. Since, according to one aspect of theinvention, the valve is useful in a variety of arteries of differentdiameters and flow conditions, each implementation can have a uniqueoptimization. By way of example only, in one embodiment, the valve hasten filaments, whereas in another embodiment, the valve has fortyfilaments. Preferably, the filament diameter is chosen in the range of0.025 mm to 0.127 mm, although other diameters may be utilized.Preferably, the pitch angle (i.e., the crossing angle assumed by thefilaments in the fully open position—the shape memory position) ischosen in the range of 100° to 150°, although other pitch angles may beused. Preferably, the Young's modulus of the filament is at least 100MPa, and more preferably at least 200 MPa.

According to another aspect of the invention, the valve is chosen tohave a pore size which is small enough to capture (filter) embolicagents in the blood stream as the blood passes through the valve. Wherelarge embolic agents (e.g., 500 μm) are utilized, it may be possible forthe filaments of the valve to act directly as a filter to preventembolic agents from passing through the valve (provided the filamentspresent pores of less than, e.g., 500 μm). Alternatively, a filter maybe added to the filament structure. Such a separate filter isparticularly useful where smaller embolic agents are utilized.

FIG. 3A shows a braid valve 203 at the distal end of a catheter 201 andhaving a filter 301 that is added to the braid structure 203. The filtercan be placed onto the braid by spraying, spinning, electrospinning,bonding with an adhesive, thermally fusing, mechanically capturing thebraid, melt bonding, or any other desired method. The filter can eitherbe a material with pores such as ePTFE, a solid material that has poresadded such as polyurethane with laser drilled holes, or the filter canbe a web of very thin filaments that are laid onto the braid. Where thefilter 301 is a web of thin filaments, the characteristic pore size ofthe filter can be determined by attempting to pass beads of differentdiameters through the filter and finding which diameter beads arecapable of passing through the filter in large quantities. The very thinfilaments can be spun onto a rotating mandrel according to U.S. Pat. No.4,738,740 with the aid of an electrostatic field or in the absence of anelectrostatic field or both. The filter thus formed can be adhered tothe braid structure with an adhesive or the braid can be placed on themandrel and the filter spun over it, or under it, or both over and underthe braid to essentially capture it. The filter can have some poresformed from spraying or electrospinning and then a secondary step wherepores are laser drilled or formed by a secondary operation. In thepreferred embodiment a material capable of being electrostaticallydeposited or spun is used to form a filter on the braid, with thepreferred material being capable of bonding to itself. The filter may bemade of polyurethane, pellethane, polyolefin, polyester, fluoropolymers,acrylic polymers, acrylates, polycarbonates, or other suitable material.The polymer is spun onto the braid in a wet state, and therefore it isdesirable that the polymer be soluble in a solvent. In the preferredembodiment, the filter is formed from polyurethane which is soluble indimethylacetamide. The polymer material is spun onto the braid in aliquid state, with a preferred concentration of 5-10% solids for anelectrostatic spin process and 15-25% solids for a wet spin process.FIG. 3B shows the valve in the deployed state, with outer catheter 202retracted proximally (as indicated by the arrow) where the braid 203 andthe filter 301 are expanded.

According to one aspect of the invention, the filter 301 has acharacteristic pore size between 10 μm and 500 μm. More preferably, thefilter 301 has a characteristic pore size between 15 μm and 100 μm. Evenmore preferably, the filter 301 has a characteristic pore size of lessthan 40 μm and more preferably between 20 μm and 40 μm. Most desirably,the filter 301 is provided with a characteristic pore size that willpermit pressurized blood and contrast agent to pass therethrough whileblocking passage of embolizing agent therethrough. By allowingregurgitating blood and contrast agent to pass through the filter in adirection from distal the valve toward the proximal end of the valve,the contrast agent may be used to indicate when the target site is fullyembolized and can serve to identify a clinical endpoint of theembolization procedure. Therefore, according to one aspect of theinvention, the valve allows the reflux of the contrast agent as anindicator of the clinical endpoint while preventing the reflux of theembolization agents at the same time. In addition, by allowing blood toflow back through the filter material, even at a relatively slow rate,backpressure on the distal side of the valve can be alleviated.

The filter 301 is also preferably provided with a hydrophilic coating,hydrophobic coating, or other coating that affects how proteins withinblood adhere to the filter and specifically within the pores of thefilter. More specifically, the coating is resistant to adhesion of bloodproteins. One coating that has been used successfully is ANTI-FOGCOATING 7-TS-13 available from Hydromer, Inc. of Branchburg, N.J., whichcan be applied to the filter by, e.g., dipping, spraying, roll or flowcoating.

By appropriate design of the pore size and use of an appropriatecoating, proteins in the blood will almost immediately fill the poresduring use. The proteins on the coated porous filter operate as apressure safety valve, such that the pores are filled with the proteinswhen subject to an initial fluid pressure greater than the blood vesselpressure, but the proteins are displaced from the pores and the poresare opened to blood flow at higher pressures such as a designatedthreshold pressure. The designated threshold pressure is determined toprevent damage to the tissue and organs, and injury to the patient.Thus, this system allows a pressure greater than the vessel pressurewhile limiting very high pressures which may be unsafe to the patient.As such, the system provides pressure regulation which is not possiblewith other occlusive devices, including balloons. Notwithstanding theadvantage of the above, it is not a requirement of the invention thatthe filter be constructed to allow either blood or contrast agent topass through in the upstream ‘reflux’ direction under any determinedpressure.

According to one aspect of the method of the invention, the valve iscapable of endovascular deployment. The valve is preferably coupled tothe distal end of a catheter. When the distal end of the catheter is inthe correct location for treatment, the valve is deployed. Preferably,with the valve deployed, embolization agents are delivered underpressure distally through the catheter and into the vessel. As discussedabove, delivery of the embolization agents in this manner will result ina pressure change that initially causes higher pressure within the valvethan upstream of the valve, thereby resulting in the valve rapidlyexpanding to assume an open position. During such expansion, the valveexpands from an initial diameter (non-deployed or non-pressuredposition) to a final diameter (its open position) which is preferably atleast twice, and more typically four to ten times the outer diameter ofthe catheter. In its open position, the valve stops embolization agentsfrom traveling upstream past the valve (between the catheter wall andthe vessel wall) in a proximal ‘reflux’ direction. According to oneaspect of the invention, the valve is preferably capable of beingretracted into its closed position after the embolization treatmentprocedure is completed.

It is important to note that the valve is a dynamic element that opensand closes based on local pressure conditions. In normal blood flowconditions when no fluid is infused through the catheter, the pressurewithin the valve and downstream of the valve is lower than the vascularpressure upstream of the valve. This pressure differential is sufficientto overcome the weak biasing force of the valve, thereby forcing thevalve into a partially closed position such that it does not contact thevascular wall and thereby permits fluid to flow in the downstreamdirection around the outside of the valve. When the fluid pressureinside and outside of the valve is substantially the same, as may occurduring the cyclic blood pressure and related flow conditions as theheart beats, the biasing force of the valve filaments causes the valveto expand into a partially expanded, but still ‘closed’ position; i.e.,the valve does not reach the vessel wall. In addition, this may occur,e.g., when a priming fluid is infused through the catheter and valve ata similar pressure to the blood pressure. When higher pressure isgenerated through the open the distal end of the catheter and inside ofthe valve, such as may occur when the embolic infusate is injected underpressure into the catheter, the valve rapidly enters a fully openposition in which it is in full contact with the vascular wall, therebypreventing reflux of embolizing agents.

By way of example, referring to FIG. 52, a prior art infusion catheteris shown. Embolic agent infused through the catheter will refluxupstream of X₁ if either or both the downstream vessel pressure at P₀ orthe catheter pressure at P₁ is greater than the upstream vessel pressureP₂. This will result in embolic agent traveling upstream past theopening of the catheter and to a location X₂, which may include upstreamand branched locations at which the agent may have deleterious effect.By contrast, turning now to FIG. 53, the system of the invention isshown. In this system, embolic agent is infused through the catheter.Provided the pressure P₁ within the catheter is greater than the vesselpressures at P₂, the valve will substantially fully and immediatelyopen. This prevents reflux of the embolic agent to a location X₂ andconstrains the agent to downstream flow toward X₀.

In addition, because the valve opens to prevent reflux of the embolicagent, significantly higher pressures can be applied at the catheter. Atsuch higher infusion pressures, (1) a larger bolus of embolic agent canbe infused, (2) the embolic agent can be driven downstream with greaterdistal penetration than otherwise possible with a standard catheter, and(3) or both. This effect is clearly shown in the results of an animalstudy in which one exemplar organ, pig kidneys, were infused with 40 μmtantalum beads (which are visible under X-rays) by each of a standardcatheter and with the system of the invention. The kidney vasculature ishierarchical toward the cortex; i.e., larger vessels are located towardthe center and smaller distal vessels branch outward toward theperiphery. After infusion, the kidneys were imaged under Micro CT, whichhas a resolution of 50 μm and is highly sensitive to the tantalum beads.Referring to FIGS. 54-55, the images indicate that the agent did notpenetrate into the smaller distal branches and instead remained in themedium sized vessels. Presumably, this is because insufficient pressurecould be applied via the catheter to overcome the backpressure from therapidly filling smaller vessels, and instead the pressure from theinfusion catheter was equalized upstream. In contrast, referring toFIGS. 56-57, the images indicate significantly deeper penetration, outto the peripheral small vessels. The system allows the embolic to beapplied under significant pressure to achieve such penetration. Further,the apparatus may be used to infuse a bolus of therapy, and then a largeinfusion of saline under pressure to create greater distal penetrationof a small dose of therapy. This is not done with prior art systems outof concern for reflux.

It is recognized that in the open state, proteins in the blood mayrapidly fill the pores of the filter valve. However, as discussed above,should a threshold pressure be reached, the filter valve is designed topermit the blood to reflux through the pores of the filter valve whilestill blocking the passage of the embolic agent. An exemplar thresholdpressure is 180 mmHg on the distal surface of the filter valve, althoughthe device can be designed to accommodate other threshold pressures.Such can be effected, at least in part, by the use of an appropriatecoating on the filter that facilitates removal of the blood proteinsfrom within the filter pores when subject to threshold pressure. Thisprevents the vessel in which the device is inserted from being subjectto a pressure that could otherwise result in damage. Nevertheless, it isnot necessary that blood and contrast agent be permitted to refluxthrough the valve.

According to one aspect of the invention, deployment of the valve iscontrolled from the proximal end of the catheter. In some embodiments, acontrol wire or a set of two or more control wires extending from theproximal end of the catheter to the distal end of the catheter may beused and controlled by the practitioner to deploy and optionally retractthe valve. In some embodiments, a control thread extending from theproximal end of the catheter to the distal end of the catheter is usedto unravel fabric covering the valve in order to deploy the valve. Insome embodiments, an outer catheter that extends the length of thecatheter to which the valve is coupled, covers the valve and duringdeployment is pulled backward to allow the valve to expand. In someembodiments, an outer sleeve that is coupled to a control element thatextends the length of the catheter, covers the valve and duringdeployment is pulled backward by the control element to allow the valveto expand. In some embodiments, the valve is coupled to a guidewire, andremoval of the catheter guidewire initiates deployment of the valve. Thecontrol wires, threads, sleeves, etc. may be of standard length,ranging, for example, from 60 cm to 240 cm long.

As previously mentioned, the deployment of the valve can be achieved ina variety of manners. As was described in FIGS. 2A-2B, the valve can bedeployed by moving an outer catheter or sleeve that covers the valve. Inthat embodiment, the valve can be recaptured by the outer catheter orsleeve by moving the catheter or sleeve distally or the deliverycatheter and valve proximally. In another embodiment, and as seen inFIGS. 4A-4C, the valve is released by irreversibly removing (unraveling)a knitted sleeve (weft knit) 402 that covers the valve 203 (shown withfilter 301). More particularly, as seen in FIG. 4A, the valve 203 isattached to the distal end of the catheter 201. On top of the valve is aweft knit sleeve 402. A control thread 401 is attached to the weft knitand extends to the proximal end of the catheter. In one embodiment theunravelable knit is composed of polyester of a thickness between 10 μmand 60 μm. The knit can be a textile sheath that is held under tension.FIG. 4B shows the deployment of the valve by pulling on the controlthread 401. In one embodiment, the thread 401 is connected to the distalend of the knit sleeve 402 and releases the valve by first removingmaterial from the distal end of the sleeve 402. As the control thread401 is pulled back and the sleeve is reduced in size, the distal end ofthe valve 203 having filter 301 is free to open. The weft knit sleeve402 may be partially or fully removed to allow the physician control ofthe diameter or length of the valve. In FIG. 4C the weft knit is morefully removed enabling more of the length of the valve 203 and filter301 to be free. In another embodiment the thread is attached to themiddle or proximal end of the sleeve, and releases the valve by firstremoving material from the proximal end or from the middle of thesleeve.

Turning now to FIGS. 5A and 5B, in another embodiment, a guidewire 501can be used to deploy the valve 503. More particularly, valve 503 isprovided with loops 502, which are attached at or near the distal end ofthe filaments of the valve 503. The loops 502 may be integral with thefilaments or may be made of a separate material and attached to thefilaments. As seen in FIG. 5A, the loops 502 are looped over the distalend of the guidewire 501 which extends through the lumen of the catheter201. The loops at the end of the valve 502 are looped around theguidewire 501 while the catheter 201 and guidewire 501 are advancedthrough the vasculature. In this manner, the distal end of the valve ismaintained in a closed position. When the guidewire 501 is withdrawnproximally as denoted by the arrow in FIG. 5B, the distal loops 502 arereleased, and the valve 503 is deployed.

According to one aspect of the invention, the valve of any embodiment ofthe invention is attached to the distal end of the catheter in any ofseveral manners. As seen in FIG. 6A, the valve 203 is attached to thecatheter 201 by a sleeve 601 which overlies the proximal end of thevalve 203 and extends proximal the proximal end of the valve 203 overthe catheter 201. FIG. 6B shows a cross-sectional view of the catheter201, valve 203, and sleeve 601. The sleeve 601 is bonded or mechanicallyheld by a heat shrink process or other mechanical process to thecatheter 201, and thus holds the distal end of the valve 203 on thecatheter 201 by trapping the distal end of the valve between thecatheter 201 and the sleeve 601.

In one preferred embodiment, the valve is fused into the catheter. Moreparticularly, as seen in FIG. 6C the valve 203 fused into the catheter201 such that at the region 602 where the valve and catheter are fused,there is at most a minimal change to the inner or outer diameter of thecatheter 201. FIG. 6D shows a cross-sectional view of the fused valve,where the catheter 201, valve 203 and fused region 602 are all of thesame diameter. Fusion of the catheter and valve can be achieved bythermally melting the valve, melting the catheter, melting both thevalve and the catheter, or by a chemical process.

Turning now to FIGS. 7A and 7B, a valve 702 composed of a singlefilament coil is seen. The coil may be made of metal or polymer, andpreferably the filament is a shape memory polymer. FIG. 7A shows a coilvalve 701 in the retracted state on a catheter 201. The coil valve isprovided with a filter 702 on its distal end. FIG. 7B shows the coilvalve in the deployed state, where the valve 701 and the filter 702 areexpanded at the distal end. Any of a variety of methods as previouslydisclosed can be used in deploying the valve.

Turning now to FIGS. 8A-8E, another embodiment of a deployment apparatus800 is shown. The deployment apparatus 800 includes a delivery catheter801, a valve 803, a deployment element 810, and a valve introducer 812.In distinction from certain prior embodiments, the delivery catheter isnot required to be advanced relative to an outer catheter or outersleeve to deploy the valve, as will become apparent from the followingdescription.

The delivery catheter 801 is preferably a 3 French microcatheter or a 4or 5 French catheter. The delivery catheter 801 is constructed of one,two or more than two layers. In one embodiment, the delivery catheter801 includes an inner liner made of, e.g., FEP or PTFE, a central braidmade of one or more of metal, polymer or liquid crystal polymer, and anouter polymeric cover made of, e.g., a polyether block amidethermoplastic elastomeric resin such as PEBAX®, polyetheretherketone(PEEK), or another suitable polymer.

The delivery catheter 801 has a distal end 805 provided with a valveseat 814 and a radiopaque marker band 816 located proximal to, distalof, or about the valve seat 814. The valve seat 814 is preferablydefined by a circumferential inner groove located at the distal end 805of the delivery catheter 801. The valve seat 814 may be defined directlyon the delivery catheter, or be bonded or fused into the deliverycatheter or to the distal end 805 of the delivery catheter. When thevalve seat 814 is defined directly on the delivery catheter 801 and thedelivery catheter is made from a multilayer construct, the valve seat814 may be defined through one or two layers, or two layers and apartial depth of a third outer layer.

The valve 803 is generally as described in any of the embodiments above.The valve 803 may be a polymer braid coated with a polymer surface, ametal braid coated with a polymer surface, or a combination of polymerand metal braid coated with a polymer surface. The polymer surface maybe a sheet, a sheet with holes drilled into it, or a mesh. The valve maybe permeable or impermeable to blood. Regardless of the construct, thevalve is a dynamic element that opens and closes based on local bloodflow conditions. The proximal portion of the valve 803 includes matingstructure 818 that can engage with the valve seat 812 at the distal end805 of the delivery catheter 801 when the valve is advanced through thedelivery catheter, as described in more detail below.

The mating structure 818 may include a shape memory polymer or elasticpolymer that can be compressed for advancement through the body of thecatheter, but which will automatically expand to seat in the valve seat814. Referring to FIGS. 8C and 8D, when the mating structure 818 isengaged at the valve seat 814, such engagement locks the valve 803relative to the delivery catheter 801 to prevent further distal movementof the valve relative to the delivery catheter and prevent the valvefrom exiting the distal end of the delivery catheter during theprocedure. The mating structure 818 may be comprised of a plurality ofindependent features, e.g., four features, which each separately engagein the valve seat. Further, the features should be small in profile,e.g., not exceeding 0.25 mm in a radial ‘height’ dimension 818 h througha center of the features, in order to maintain a low profile within thedelivery catheter 801 as the valve 803 is advanced through the deliverycatheter and also after the valve is engaged relative to the valve seat814. By way of one example, the mating structure on the valve 803includes a plurality of radiopaque metal slugs 818 a-d bonded, fused,crimped or otherwise attached to the valve 803 and that can be receivedin the valve seat 814. The valve seat 814 may additionally include aradiopaque marker. In this manner, alignment of the valve with the valveseat can be visualized under fluoroscopy. The slugs 818 a-d haveproximal and distal surfaces 819 a, 819 b that are shaped to prevent theadvancement or withdrawal of the valve 803 once the slugs are receivedin the valve seat. That is, the surfaces 819 a, 819 b may extend inplanes perpendicular to the longitudinal axis of the delivery catheter.The proximal portion of the valve 803 is preferably constrained by theinner wall 801 a of the delivery catheter 801 so as to define an innerdiameter 803 through the valve.

The deployment element 810 is a push wire preferably generally similarin construction to a conventional guide wire. The outer diameter of thedistal end 810 a of the push wire is larger than the inner diameter ofthe proximal end of the valve 803. As a result, the push wire 810 can beused to provide a pushing force at the proximal portion 803 a of thevalve 803 and advance the valve through the delivery catheter 801; i.e.,the distal end 810 a of the push wire 810 and proximal portion 803 a ofthe valve are relatively sized so that the push wire 810 will not freelyextend through the valve 803. When the proximal portion 803 a isconstrained by inner wall 801 a, the push wire 810 may include a polymerbead or metal bead to increase its distal end diameter and facilitateapplication of a pushing force on the valve. Additionally oralternatively, a cylindrical or tubular element may be fused or bondedonto the distal end of the push wire to aid in application of a pushingforce against the valve. Additionally or alternatively, one or moremetal or polymeric coils may be provided at the distal end of the pushwire to increase its outer diameter. Any feature added to the distal endof the push wire should maintain trackability of the push wire. The pushwire 810 is preferably made from a radiopaque material or contains oneor more radiopaque markers, such as of platinum, along its length.

The valve introducer 812 is a polymeric tube made, e.g., from PTFE. Theintroducer 812 is preferably 1 cm to 50 cm in length and may optionallybe provided with a handle at its proximal end (not shown) to facilitatemanipulation thereof. As shown in FIG. 8E, the valve 803 and preferablyat least a portion of the push wire are held within the introducer 812,with the distal end of the valve 803 held in a collapsed configuration.The introducer 812, by retaining the valve 803 in the collapsedconfiguration, presents the valve in a size suitable for advancementthrough the delivery catheter 801. The introducer 812 has an innerdiameter sufficiently large to contain the collapsed valve 803 and thepush wire 810. The introducer 812 has an outer diameter smaller than theinner diameter of the infusion port 807 at the proximal end of thedelivery catheter, so that the introducer can be advanced into theinfusion port. In one embodiment, the inner diameter is 0.89 mm and theouter diameter is 0.96 mm.

Referring to FIGS. 8C and 8D, in use of the apparatus 800, a standardguidewire (not shown) is advanced through the vasculature of the patientahead to a desired location of treatment. The delivery catheter 801 isadvanced over the standard guidewire to the desired location. Once thedelivery catheter 801 is at the desired location, the standard guidewireis removed from the delivery catheter and patient. The valve introducer812 is then inserted into the infusion port of the delivery catheter801. Depending on the length of the valve introducer 812, it mayfunction as a guide for valve insertion solely at the proximal end ofthe delivery catheter or as a guide along a substantial length of thedelivery catheter. The push wire 810 is then distally advanced relativeto the introducer 812 to push the valve 803 (in an undeployedconfiguration) within the delivery catheter 801 toward the valve seat814. When the valve 803 approaches the valve seat 814, the matingstructure 818 automatically expands into and engages the valve seat 814to lock the valve 803 relative to the distal end 805 of the deliverycatheter 801. In the locked configuration, the valve is deployed at thedistal end of the delivery catheter. The push wire 810 is then withdrawnfrom the delivery catheter 801.

Embolic agents are then infused through the delivery catheter 801 andthe valve 803. The valve 803 functions as described above. That is, asthe embolic agents are infused, the valve 803 enables forward flow butprevents reverse flow (reflux) of embolic agents in the blood vessel inwhich the delivery catheter is inserted. As a result of not using a tubewithin a tube construct during infusion of embolic agents (i.e., adelivery catheter with an outer sleeve), as described in various aboveembodiments, a larger delivery catheter can be used to provide greaterflow of embolic agents to the treatment site. After infusion iscomplete, the delivery catheter 801, along with the valve 803 at itsdistal end 805, is retracted from the patient.

It is also appreciated that while positive engagement between a valveand valve seat is desired, it is not necessary. That is, providedalignment of the valve relative to the distal end of the catheter can befluoroscopically visualized, such as with the use of respectiveradiopaque markers, the valve can be manually retained at theappropriate location relative to the catheter.

Another embodiment similar to deployment apparatus 800 includes adeployment element constructed of a thin wire attached to the valve. Thewire preferably has a diameter of 0.025 mm to 0.125 mm, and may be astandard wire or a flattened wire. A flattened wire may more closelycorrespond to the inner surface of the catheter to limit any obstructionof the lumen of the catheter. In use, the thin wire advances the valveto the valve seat and then remains attached to the valve and within thecatheter during infusion of the embolic agent.

Turning now to FIGS. 9A-9D, another embodiment of a deployment apparatus900 is shown. The deployment apparatus 900 is substantially similar toapparatus 800 and includes a delivery catheter 901, a valve 903, a pushwire 910 and a valve introducer (as described with respect to introducer812). The difference between apparatus 900 and prior described apparatus800 is the mating structure 918 provided to the valve to lock the valverelative to the valve seat. In FIGS. 9A and 9B the mating structure 918is a proximal ring-shaped flange that is radially compressed orotherwise deformed to a size permitting advancement through the deliverycatheter as its is pushed by the push wire 910. As shown in FIGS. 9C and9D, once the push wire 910 delivers the valve 903 to the distal end 905of the delivery catheter 901, the flange 918 expands into the valve seat914 once located at the valve seat to lock the valve 903 relative to thevalve seat 914. The ring-shaped flange 918 may be defined by an elasticelement coupled to the braid of the valve or a metal braid or metalstent portion of the valve that has a much higher expansion force than aremainder of the valve.

FIGS. 10A-12B illustrate additional embodiments of a flange matingstructure that can be used on the valve for locking engagement between avalve and a valve seat. FIGS. 10A and 10B show a flange 1018 having aproximal end which in cross-section appears L-shaped or J-shaped andthat engages within the valve seat 1014. FIGS. 11A and 11B show a flange1118 having an abutting front surface 1118 a and a rear bevel 1118 b(appearing as a barb in cross-section) such that the flange has aproximal taper (i.e., a smaller proximal diameter and a relativelylarger distal diameter). This structure facilitates proximal release ofthe flange 1118 from the valve seat 1014 for removal of the valve 1103from the delivery catheter 1101, particularly suitable in conjunctionwith an embodiment of the apparatus provided with a valve retractionelement, discussed further below. FIGS. 12A and 12B show a flange 1218comprised of an o-ring, and wherein the valve seat 1214 is in the formof a circular channel in which the o-ring is captured. FIGS. 13A and 13Billustrate another embodiment of a valve seat 1314 at the distal end ofthe delivery catheter 1301 and corresponding mating structure 1318 on avalve 1303. The valve seat 1314 and mating structures 1318 are ‘keyed’with multiple longitudinally displaced structures that enhanceengagement between the valve 1303 and the valve seat 1314, but thatprevent locking engagement until the structures are in properlongitudinal alignment with each other. By way of the example shown, thevalve seat may include a plurality of longitudinally displaced channels1314 a, 1314 b, wherein a distal channel 1314 a has a greater width thana proximal channel 1314 b. The mating structure 1318 includes a distalflange 1318 a sized to be received in the distal channel 1314 a but toolarge to be received in the proximal channel 1314 b. The matingstructure also includes a proximal flange 1318 b that is appropriatelysized for being received and captured by the proximal channel 1314 b.When the proximal and distal flanges 1318 a, 1318 b are aligned with theproximal and distal channels 1314 a, 1314 b, the flanges expand into therespective channels and lockingly engage the valve 1303 relative to thedistal end of the delivery catheter 1301. In any of the embodimentsdescribed above, the flange may include a circumferentiallyuninterrupted element or be comprised of separate elements radiallydisplaced about the proximal portion of the valve. Furthermore, whilethe valve seat is shown as comprising ‘negative’ space and the matingstructure as one or more elements that expand into such space, it isappreciated that the structure for the valve seat and mating structuremay be reversed; i.e., such that the valve seat comprises elements thatextend into the lumen of the delivery catheter and the mating structurebeing a groove or other negative space about the proximal end of thevalve. However, such a reverse configuration is less desired as itreduces the diameter of the infusion path at the distal end of thedelivery catheter.

Turning now to FIGS. 14A and 14B, another embodiment of a deploymentapparatus 1400 is shown. The deployment apparatus 1400, which includessimilar elements to apparatus 800, has a delivery catheter 1401, a valve1403, a push wire 1410 and a valve introducer (as described with respectto introducer 812). In addition, the apparatus 1400 includes aretraction element 1420 that is attached to the proximal portion of thevalve 1403, and more preferably to the mating structure 1418 thereof, toapply a release and retraction force to the valve to thereby disengagethe valve from the valve seat and withdraw the valve through thedelivery catheter.

The retraction element 1420 is a pull wire attached to the matingstructure 1418. The pull wire 1420 may be flattened or otherwise formedsuch that it conforms close to the inner surface 1401 a of the deliverycatheter 1401 to maximize the usable space within the lumen of thedelivery catheter for delivery of the embolic agent. The pull wire 1420should have sufficient mechanical strength in tension to release andwithdraw the valve 1403 from the delivery catheter. However, it isappreciated that the pull wire 1420 is not required to have highcompressive stiffness, as the push wire 1410 extends parallel to thepull wire 1420 and performs the function of advancing the valve to thedistal end of the delivery catheter.

Use of the apparatus is similar to apparatus 800. The valve 1403, pushwire 1410 and pull wire 1420 are all surrounded with an introducer (notshown) that facilitates introduction of such elements into the infusionport of the delivery catheter. The push wire 1410 advances the valve1403 and pull wire 1420 out of the introducer and to the distal end ofthe delivery catheter 1401. Once the valve 1403 engages the valve seat1414, the push wire 1410 is withdrawn from the delivery catheter 1401.Embolic agents are then infused through the delivery catheter 1401 totreat the patient. After the embolic agents have been infused, the valve1403 can be withdrawn into the delivery catheter 1401 by applying asufficient tensile force on the pull wire 1420 to release the valve 1403from the valve seat 1414 and retract it into the delivery catheter 1401.The delivery catheter is then removed from the patient. Optionally, thepull wire 1420 may be used to completely withdraw the valve 1403 fromthe delivery catheter 1401 prior to removing the delivery catheter fromthe patient.

In addition to a single pull wire, the retraction element may take otherforms which may be similarly used to withdraw the valve from thedelivery catheter after infusion of the embolic agent. For example,referring to FIGS. 15A and 15B, the retraction element includes aplurality of pull wires, such as the pair of pull wires 1520 a, 1520 bshown. In addition, referring to FIGS. 16A and 16B, the retractionelement may comprise a tubular retraction braid 1620 of multiple metalwires or polymeric filaments. The braid 1620 may be made from stainlesssteel, Elgiloy®, Nitinol or another elastic material. The tubular braid1620 may have a predefined diameter that is the same or larger than thediameter of the lumen of the delivery catheter. In this manner theretraction braid can be held taut against the pushing force of the pushwire 1610 in order to decrease it to a diameter smaller than thediameter of the lumen of the delivery catheter 1601. Once the push wire1610 advances the valve 1603 to the valve seat 1614, the tension isreleased from the braid 1620 to permit the braid to be held outwardagainst the inner wall 1601 a of the delivery catheter 1601. Further,referring to FIGS. 17A and 17B, a retraction braid 1720 may be coatedwith a polymeric coating 1722. The polymeric coating 1722 may include,e.g., one or more of polyurethane, polyamide, polyimide, PTFE or FEPsuch that the retraction element defines a catheter body. It is notedthat in embodiments using a retraction element separate from a pushwire, the retraction element can be designed with a low compressivestrength, as the separate push wire 1710 performs advancement of boththe valve and the retraction element through the delivery catheter.

As yet another alternative, the push wire and retraction element may becomprised of a single element having sufficient compressive and tensilestrengths to advance the valve to the valve seat and retract the valvefrom the valve seat at the conclusion of the procedure. Such singleelement should be of a design which retains usable space within thelumen of the delivery catheter to permit sufficient infusion of embolicagents.

Referring to FIG. 18A, another deployment apparatus 1800 is shown. Thedeployment apparatus 1800 has a delivery catheter 1801, a valve 1803, apush wire 1810, a retraction element in the form of a polymer-coatedbraid 1820, and a valve introducer (as described with respect tointroducer 812). The valve seat 1814 is defined by the distal end of thedelivery catheter 1801. The mating structure 1818 of the valve seat 1814is compressed for advancement through the delivery catheter. As shown inFIG. 18B, once the mating structure 1818 passes through the distal end1805 of the delivery catheter 1801, the mating structure expands intocontact with the valve seat 1814. The retraction element 1820 maintainstensile force on the valve 1803 to hold the valve 1803 against the valveseat 1814.

In another embodiment of the invention, no deployment element isrequired. The valve is advanced through the catheter to a valve seatusing hydraulic pressure. Any of the valve designs described above withrespect to FIGS. 8-17 are provided within the catheter, e.g., using anintroducer. Then, via the infusion port, a bolus of saline orheparinized saline is injected into the catheter behind the valve toforce the valve to the distal end. U.S. Pat. No. 6,306,074, which isincorporated by reference herein, describes the use of hydraulicpressure to advance treating elements such as radioactive therapeuticseeds through a catheter to a delivery location. Hydraulic pressure cansimilarly be applied to advance the valve, taking into accountfrictional forces between the valve and inner surface of the catheter,blood pressure and gravitational force. It is appreciated that when thevalve is within the catheter, it is sufficiently radially collapsed toprovide an adequate barrier within the catheter on which the bolus ofsolution acts.

Another embodiment of a delivery apparatus 1900 is shown at FIG. 19. Thedelivery apparatus 1900 includes an outer catheter 1901 having aproximal end (not shown) and a distal end 1903, an inner catheter 1904extendable through the outer catheter, and a valve 1905 situated in thedistal end 1903 of the outer catheter 1901. The valve 1905 includes aproximal expandable framework 1906, one or more control members 1908 (or1908 a, 1908 b in FIG. 20) coupled to the proximal end of the framework1906, a central collar 1910 at the distal end of the framework 1906, andone or more valve flaps 1912 extending distally from the collar 1910.The framework 1906 and collar 1910 are preferably made from form anexpandable structure. Both the framework 1906 and collar 1910 arepreferably made of a material have shape memory or other spring-likeexpansible properties so that they are self-expanding, or areconstructed of a non-shape memory or non-springy material that can beexpanded under force, e.g., by balloon expansion as described furtherbelow. The framework 1906 and collar 1910 may be a mesh of metal wire orpolymeric filaments, a wire or tubular stent structure, or othersuitable structure. The framework 1906 and collar 1910 may be integrallyformed together, or separately formed and then coupled together. Thecollar 1910 is sufficiently expansible and appropriately sized tocontact the inner wall of an artery when partially or fully expanded.The valve flaps 1912 are preferably constructed in a manner similar toabove described valve structures. For example, the valve flaps 1912 mayeach comprise a filamentary structure or other mesh overlaid with apolymer coating. The valve flaps may be structured to permit bloodand/or contrast agent to pass through the material thereof, or may beimpermeable to such fluids. The valve flaps 1912 may include two flaps1912 of equal size in a duck-bill formation (FIG. 21A), three or moreflaps 1912′ of equal dimension (FIG. 21B), or flaps 1912 a″, 1912 b″ ofdifferent size (FIG. 21C). In each embodiment, distal portions of theflaps may be shaped (as shown by broken lines) to together define acircular opening 1913 for passage of the inner catheter 1904therethrough. The control member 1908 may advance and retract the valve1905 relative to the outer and inner catheters 1901, 1904 between housedand deployed configurations. Alternatively, the valve 1905 can becoupled directly to the inner catheter 1904, with movement of the innercatheter relative to the outer catheter 1901 effecting movement of thevalve 1905 between a housed configuration and a deployed configuration.In a first housed configuration, the framework 1906 and collar 1910 areradially constrained by the outer catheter 1901, and the flaps 1912 areheld closed against each other (prior to insertion of the inner catheter1904 through the valve) (FIGS. 21A-21C). In a second housedconfiguration shown in FIG. 19, the framework 1906, collar 1910, andvalve 1905 remain radially constrained within the outer catheter 1901,and the inner catheter 1904 is extended through the valve flaps 1912. Ina first deployed configuration, operation of the control member 1908distally advances the valve 1905 out of the distal end of the outercatheter 1901, and the collar 1910 is permitted to self-expand until theproximal ends of the valve flaps 1912 are adjacent the arterial wall1920 (FIG. 22). Alternatively, where the valve 1905 is coupled relativeto the inner catheter 1904, the inner catheter functions as the controlmember and the inner catheter and outer catheter are moved relative toeach other to advance the valve out of the distal end of the outercatheter into the same deployed configuration. In the first deployedconfiguration, the valve 1905 is fluid opening is opened by downstreamfluid pressure 1922 a on the proximal side of the valve. The embolizingagent 1924 is infused through the inner catheter 1904. When the fluidpressure changes such that higher pressure 1922 b is located on thedistal side of the valve, such as may occur during a change in bloodpressure or by user-operation upon infusion of an embolic agent 1924,the valve 1905 dynamically changes due to the changes in pressureconditions to a second deployed configuration in which the distal end ofthe valve flaps 1912 close against the inner catheter 1904 (FIG. 23).This prevents any embolizing agent from passing back beyond the valve.

Turning now to FIG. 24, another embodiment of a delivery apparatus 2000,substantially similar to delivery apparatus 1900, is provided with avalve 2005. The valve 2005 includes a proximal expandable framework2006, optionally one or more control members 2008 a, 2008 b coupled tothe proximal end of the framework 2006, a central collar 2010 at thedistal end of the framework 2006, and a tubular valve sleeve 2012. Thesleeve 2012 is preferably constructed in a manner similar to any abovedescribed valve, e.g., with a polymer-coated filamentary construct, butmay be of other construction. In a housed configuration, the sleeve 2012resides between the outer catheter 2001 and inner catheter 2004 of thedelivery apparatus 2000, with the inner catheter 2004 extending throughthe sleeve. The sleeve 2012 may be advanced relative to the outercatheter 2001 into a deployed configuration by mounting it relative tothe inner catheter 2004 and advancing the inner catheter relative to theouter catheter, or alternatively by operation of the control members2008 a, 2008 b to move the sleeve relative to both the outer catheter2001 and the inner catheter 2004. Regardless of how the collar 2010 ofthe valve 2005 is freed of the outer catheter, once freed the collar2010 expands to contact the arterial wall 2020 and deploy the valve2012. In a first pressure condition 2022 a in which a higher pressure islocated upstream of the valve sleeve 2012, the blood may flow betweenthe valve and the inner catheter (FIG. 25). In a second deployedconfiguration, resulting when the pressure 2022 a within the bloodvessel 2020 changes to define a higher pressure condition downstream ofthe valve sleeve 2102, the valve sleeve 2012 closes against the innercatheter 2004 (FIG. 26).

Turning now to FIG. 27, another embodiment of a delivery apparatus 2100is shown. The delivery apparatus 2100 includes a valve 2105 coupled to acatheter 2101. The valve 2105 includes a plurality of struts 2116coupled at their proximal ends by a collar 2117. A suitable filtermaterial 2118 extends between the struts 2116. The delivery apparatus2100 also includes a guard 2126 coupled to the catheter 2101 thatshields the arterial wall 2120 from the distal ends of the struts 2116when the valve 2105 is in a non-deployed configuration. The deliveryapparatus 2100 includes a control member in the form of a balloon 2124that, when expanded, applies a radial force to the struts thatsufficiently flexes the struts to release the valve from the guard 2126.This results in the valve 2105 entering a deployed configuration. Theballoon 2124 may be expanded via use of a dedicated lumen of the innercatheter 2104, a distinct inflation catheter or via any other suitablesystem (such as that described below with respect to FIGS. 30-32). Inthe deployed configuration, when a higher fluid pressure condition 2122a is located upstream of the valve, forward flow of blood is permittedabout the exterior of the valve (FIG. 28). However, when an embolicagent is infused, e.g., at relatively high pressure, a higher fluidpressure condition is defined downstream of the valve, and the valve2105 dynamically and rapidly responds to the changing flow conditionsand fully opens to the arterial wall 2120 preventing flow of embolizingagent past the valve (FIG. 29).

Turning now to FIGS. 30 to 32, another embodiment of a deliveryapparatus 2200 is shown. A catheter 2201 includes an outer controlmember balloon 2234. A valve 2205 is provided over the balloon 2234 andincludes filtering material 2212 extending across circumferentiallydisplaced struts 2216. The balloon is positioned radially centeredbetween the struts. The balloon 2224 includes a pressure valve 2235 incommunication with the lumen 2228 of the catheter 2201. A guidewire 2240provided with an occlusive tip 2242 is advanced through the lumen 2228of the catheter 2201. The occlusive tip 2242 is advanced past thepressure valve 2235 (FIG. 31). An injectate 2234, such as saline, isthen injected into the catheter lumen 2228. Referring to FIG. 32,sufficient fluid and pressure are provided to cause the injectate toenter the pressure valve 2235 and fill the balloon 2234. The balloon2234 fills to high pressure and then seals to prevent leakage to lowpressure conditions. As the balloon 2234 fills to a high pressure state,it contacts the valve 2205 to move the valve to a deployedconfiguration. The guidewire 2240 may then be withdrawn from thecatheter 2201. The valve is then used as described above in conjunctionwith the infusion of an embolizing agent through the catheter 2201.After completion of the procedure, the catheter 2201 can be drawn backinto an outer catheter (not shown) and such that contact between thevalve 2205 and the distal end of the outer catheter will overcome thepressure valve 2235 and cause the pressure valve to release, the balloon2234 to deflate and the valve to re-assume a non-deployed configurationfor withdrawal from the patient.

Referring now to FIG. 33, another embodiment of a delivery apparatus2300 is shown. The apparatus includes an outer catheter 2301, an innercatheter 2304 extending through the outer catheter, and valve 2305comprising an expandable wire framework 2306 coupled to the innercatheter 2304 or operable via independent control members 2308, anexpandable collar 2310 coupled to the framework, a tapered first sleeveportion 2311 extending from the collar, and a second sleeve portion 2312extending from the first sleeve portion. In a housed configuration (notshown), the inner catheter 2304, framework 2306, control members 2308,collar 2310 and sleeve portions 2311, 2312 are held within the outercatheter 2301 and advanced to the location of interest within the artery2320. In a deployed configuration, the inner catheter 2304 is advancedout of the distal end of the outer catheter 2301 and the control members2308 are operated from the proximal end of the apparatus to deploy theframework 2306, collar 2310 and sleeves 2311, 2312 out of the outercatheter 2301 and over the inner catheter 2304. The collar 2310 expandsthe proximal end of the tapered first sleeve 2311 adjacent the arterialwall 2320. During forward blood flow 2322 a which occurs when arelatively higher pressure condition is located upstream of the valvethan downstream of the valve, the blood flows between the inner catheter2304 and the sleeves 2311, 2312, similar to air flowing through awindsock. However, when the fluid pressure condition changes, withhigher pressure downstream than upstream, at least the second sleeve2312 is structured to collapse in response to prevent reverse flow 2322b of embolizing agent 2324 through the sleeves 2311, 3212. Agent 2324contacts the exterior of the sleeves 2311, 2312 but cannot pass through.

Turning now to FIGS. 34 through 36, another embodiment of a deliverydevice 2400 is shown. The delivery device 2400 includes a control member2408 with a self-expanding shape memory loop (or collar) 2410 at itsdistal end. A valve 2412 extends from the loop 2410. The valve 2412 hasan open distal end 2413. The control member 2408 is operated to advancethe valve 2412 to the distal end 2403 of an outer catheter 2401 which isadvanced to the arterial location of interest. Referring to FIG. 35, thecontrol member 2408 is then operated to advance the loop and valve outof the distal end 2403 of the outer catheter 2401, with the loopautomatically expanding and causing the proximal end of the valve 2412to be positioned against or adjacent the arterial wall 2420. Then, asshown in FIG. 36, an inner catheter 2404 is advanced through the outercatheter 2401 and completely through the open distal end 2413 of thefilter valve 2412. Embolizing agent 2424 is infused through the innercatheter 2404. Blood may flow in the forward direction between the innercatheter 2404 and filter valve 2412. During retrograde blood flow, suchas when the pressure is increased through the inner catheter 2404, theloop 2410 retains its diameter against the arterial wall 2420, but thedistal and central portions of the filter valve 2412 dynamicallycollapses against the inner catheter 2404 in response to the changingpressure preventing reverse flow of embolizing agent 2424 past thevalve.

Referring now to FIG. 37 another embodiment of a delivery device 2500 isshown. The delivery device 2500 includes a catheter 2501, a first collar2530 about the catheter 2501 and coupled to the catheter or a firstcontrol member 2532, a second collar 2534 displaced from the firstcollar 2530 and located about the catheter and coupled to a secondcontrol member 2536, a plurality of struts 2516 extending between thefirst and second collars 2530, 2534, and a valve sleeve 2512 extendingover at least a portion of the struts 2516 and preferably the secondcollar 2534. Referring to FIG. 38, in operation, when the second controlmember 2536 is retracted relative to the catheter 2501 and/or firstcontrol member 2532 (i.e., whichever to which the first collar 2530 iscoupled), the struts 2516 are caused to bow outwards thereby moving theproximal end of the valve sleeve 2512 against the arterial wall 2520.Embolizing agent 2524 may be injected through the catheter 2512.Forwardly advancing blood 2522 a may flow between the valve sleeve 2512and the catheter 2501. Referring to FIG. 39, when there is a rapidchange in pressure against on the valve sleeve 2512, with higherpressure located on the downstream side, the valve sleeve 2512dynamically reacts collapsing against the catheter 2501 to preventretrograde flow of embolizing agent 2524 in the upstream direction 2522b. The delivery device 2500 may be collapsed for withdrawal by movingthe first control member 2532 proximally relative to the second controlmember 2536 to straighten the struts 2516 and thereby reduce thediameter of the valve sleeve 2512 (FIG. 40).

It is appreciated that it in any of the embodiments described above itmay be desirable to controllably flush the outer catheter through aroute that exits behind the valve. Such flush may include a contrastagent, saline, etc. Turning now to FIG. 41, one embodiment of a flushvalve includes one or more open slits 2640 in the outer catheter 2601. Aside stop 2642 is provided in the annular space between the outer andinner catheters 2601, 2604. Alternatively, the stop 2642 may be providedagainst an outer catheter 2601 in which no inner catheter is provided.The side stop 2642 is coupled at the distal end of a control member2644. In a closed state, the proximal end of the control member 2644 ismanipulated to position the side stop 2642 in obstruction of the openslits 2640 to prevent fluid passage therethrough. To permit flush, theproximal end of the control member 2644 is manipulated to position theside stop 2642 either proximal or distal (shown) relative to the openslits 2640 so that fluid may be flushed therethrough. Turning now toFIG. 42, another embodiment of a flush system is shown incorporatingslit valves 2740 in the outer catheter 2701. Such slit valves 2740 arenormally in a closed configuration. However, upon application of a flushunder pressure, the slit valves 2740 are opened and the flush ispermitted to escape the catheter (FIG. 43).

Turning now to FIG. 44, another embodiment of a valve deploymentapparatus 2800 is shown. The apparatus 2800 includes two longitudinallydisplaced microcatheters 2801, 2802 and a dynamic valve 2805 locatedtherebetween. More particularly, the more proximal first microcatheter2801 is a “hi-flo” microcatheter preferably having an inner diameter of0.69 mm and an outer diameter of 0.97 mm and includes a proximal luer2803 or other suitable connector at its proximal end 2801 a and has adistal end 2801 b. The distal second microcatheter 2802 preferably has aproximal end 2802 a with a proximal face 2802 c, a smaller innerdiameter of 0.53 mm, and the same 0.97 mm outer diameter as the firstmicrocatheter. The valve 2805 preferably comprises a braid that is fusedat its proximal end 2805 a to the distal end 2801 b of the firstmicrocatheter 2801 and at its distal end 2805 b to the proximal end 2802b of the second microcatheter 2802. The braid is naturally biased toradially self-expand from an undeployed state to a deployed state,wherein the valve in the undeployed state (described below) has adiameter approximately equal to the outer diameter of the first andsecond microcatheters, and into the deployed states has a diametersubstantially greater. The braid includes a proximal portion 2805 c thatis polymer coated as described with respect to several valves describedabove, whereas a distal portion 2805 d of the braid is uncoated andforms an open design permitting fluid to flow therethrough.

The apparatus 2800 further includes a thin-walled tubular elongatemember 2850 preferably having an inner diameter of 0.53 mm and an outerdiameter of 0.64 mm. The tubular member 2850 is most preferably in theform of a wire coil 2852 preferably with an axially extending peripheralwire 2854 or oversheath 2856 for longitudinal stability. The coiltubular member has a proximal end 2850 a provided with a hub 2858 forlocking relative to the luer connector 2803, such as a tuohy borstadapter and a distal end 2850 b. When the coil tubular member 2850 isinserted into the luer connector 2803, through the first microcatheter2801, and through the valve 2805, its distal end 2850 b abuts theproximal face 2802 c of the second microcatheter 2802. The coil tubularmember 2850 is sized such that when fully advanced into the firstmicrocatheter 2801, the proximal end 2802 a of the second microcatheter2802 is displaced from the distal end 2801 b of the first microcatheter2802 a sufficient distance to apply a tensile force on the valve tocause the valve to elongate and constrict in diameter to a significantlysmaller non-deployed diameter suitable for advancement through thevessel. The apparatus 2800 may be presented in this configuration in anas manufactured and/or sterilized package.

Referring to FIG. 45, a standard 0.356mm guidewire 2860 is provided foruse with the apparatus 2800. The guidewire 2860 is inserted through thehub 2858 and luer connector 2803 and through the first microcatheter2801, the valve 2805 and the second microcatheter 2802. The guidewire2860 is advanced to the site of the emboli and the apparatus 2800 isthen tracked over the guidewire to the site.

Referring to FIG. 46, the guidewire 2860 is shown withdrawn, and thecoil tubular member 2850 is released from the luer connector 2803 andremoved from the first microcatheter 2801, allowing the valve 2805 toexpand to the arterial wall (not shown). Embolizing agent 2824 is theninfused through the first microcatheter 2801 and exits through theuncoated distal portion 2805 d of the valve and the second microcatheter2802. Importantly, the valve 2805, even through coupled at its distalend to the second microcatheter, is a dynamic valve rapidly adjusting topressure conditions resulting from changing blood pressure in systoleand diastole and the pressure of infused embolic agent. Thus, during theforward flow of blood in systole; i.e., when fluid pressure is higherupstream of the valve than downstream of the valve, the coated proximalportion 2805 c of the valve collapses to permit the blood to flow aroundthe valve. Further, during e.g., retrograde blood flow upon infusion ofembolic agent, the coated proximal portion of the valve opens againstthe arterial wall preventing passage of any of the embolizing agent.

Turning to FIG. 47, after the procedure, the device comprising themicrocatheters 2801, 2802 and valve 2805 may simply be withdrawn fromthe artery which will automatically collapse the valve. However, as anoption, the coil tubular member 2805 may be reinserted to aid incollapse and the guidewire 2860 may also optionally be reinserted tofacilitate reverse tracking out of the patient. Regardless of the methodof removal, it is appreciated that any embolizing agent 2824 remainingin the valve upon collapse of the valve will remain trapped in the valvefor retrieval as the braid angle will be reduced in size upon collapseto define openings too small for the embolizing agent to pass through.

Turning now to FIGS. 48 and 49, another embodiment of a valve deploymentapparatus 2900, substantially similar to the deployment apparatus 2800,is shown. The apparatus 2900 includes two longitudinally displacedmicrocatheters 2901, 2902 and a dynamic valve 2905 located therebetween.More particularly, the more proximal first microcatheter 2901 is a“hi-flo” microcatheter preferably having an inner diameter of 0.69mm andan outer diameter of 0.97 mm and includes a connector 2903 at itsproximal end 2901 a and has a distal end 2901 b. The distal secondmicrocatheter 2902 preferably has a proximal end 2902 a with a proximalface 2902 c, a smaller inner diameter of 0.53mm, and the same 0.97mmouter diameter as the first microcatheter. The valve 2905 preferablycomprises a braid that is fused at its proximal end 2905 a to the distalend 2901 b of the first microcatheter 2901 and at its distal end 2905 bto the proximal end 2902 b of the second microcatheter 2902. The braidincludes a proximal portion 2905 c that is polymer coated as describedwith respect to several valves described above, whereas a distal portion2905 d of the braid is uncoated and forms an open design permittingfluid to flow therethrough.

The apparatus 2900 further includes an elongate member such as aguidewire 2960. The guidewire 2960 is preferably a 0.45mm diameterguidewire, but may be other dimensions, and includes a hub 2958 adjacentits proximal end 2960 a and a preferably radiopaque marker band 2962adjacent its distal end 2960 b. The marker band 2962 is larger than theinner diameter of the second microcatheter and is thus adapted to abutagainst the proximal face 2902 c. A fixed length is indicated, whetherby actual length, indicia, or stops between the guide wire from theproximal 2901 a end of the first microcatheter 2901 or the distal end ofthe marker band 2962. The guidewire is inserted through the firstmicrocatheter such fixed length so that the marker band is abuttedagainst proximal face of the second microcatheter; this results in thevalve entering the collapsed configuration. The apparatus with guidewireis then advanced to the target. Once at the target the guidewire isremoved from the apparatus.

Referring to FIG. 50, the apparatus in use is substantially similar tothat described above with respect to FIG. 46. The valve 2905 expands tothe arterial wall (not shown). Embolizing agent 2924 is then infusedunder pressure through the first microcatheter 2901 and exits throughthe uncoated distal portion 2905 d of the valve and the secondmicrocatheter 2902. Importantly, the valve 2905, even through coupled atits distal end to the second microcatheter, is a dynamic valve rapidlyadjusting to pressure conditions resulting from changing blood pressurein systole and diastole and the pressure of infused embolic agent. Thus,during the forward flow of blood in systole; i.e., when fluid pressureis higher upstream of the valve than downstream of the valve, the coatedproximal portion 2905 c of the valve collapses to permit the blood toflow around the valve. Further, during e.g., retrograde blood flow uponinfusion of embolic agent, the coated proximal portion of the valveopens against the arterial wall preventing passage of any of theembolizing agent.

Turning to FIG. 51, after the procedure, the device comprising themicrocatheters 2901, 2902 and valve 2905 can be withdrawn by simplyretracting it from the artery which will cause collapse of the valve.However, optionally, the guidewire 2960 may be reinserted to collapsethe valve 2905. It is appreciated that any embolizing agent 2924remaining in the valve upon collapse of the valve will remain trapped inthe valve for retrieval as the braid angle will be reduced in size uponcollapse to define openings too small for the embolizing agent to passthrough.

In any of the embodiments described herein, the components of the valvemay be coated to reduce friction in deployment and retraction. Thecomponents may also be coated to reduce thrombus formation along thevalve or to be compatible with therapeutics, biologics, or embolics. Thecomponents may be coated to increase binding of embolization agents sothat they are removed from the vessel during retraction.

According to one aspect of the invention, the catheter body and mesh maybe separately labeled for easy visualization under fluoroscopy. Thecatheter body can be labeled by use of any means known in the art; forexample, compounding a radio-opaque material into the catheter tubing.The radio-opaque material can be barium sulfate, bismuth subcarbonate orother material. Alternatively or additionally, radio-opaque rings can beplaced or crimped onto the catheter, where the rings are made ofplatinum, platinum iridium, gold, tantalum, and the like. The valve maybe labeled by crimping a small radio-opaque element such as a ring onone or a plurality of filaments. Alternatively or additionally,radio-opaque medium can be compounded into the materials of the braidand the filter. Or, as previously described, one or more of thefilaments may be chosen to be made of a radio-opaque material such asplatinum iridium.

In certain embodiments, the valve is attached to a catheter which may bea single lumen or a multi-lumen catheter. Preferably, the catheter hasat least one lumen used to deliver the embolization agents. According toother embodiments, however, the catheter may provided with a lumen whicheither serves to store the valve before deployment or through which thevalve can be delivered. Where control members are utilized to controldeployment of the valve, one or more additional lumen may be provided,if desired, to contain the control wires for deployment and retraction.Alternatively, the catheter about which the control members extends mayinclude longitudinal open channels through which the control wires mayextend. An additional lumen may also be used to administer fluids, e.g.,for flushing the artery after the administration of embolization agents,or for controlling a balloon which could be used in conjunction with thevalve.

The above apparatus and methods have been primarily directed to a systemwhich permits proximal and distal flow of biological fluid (e.g., blood)within a body vessel, and which prevents reflux of an infusate past thevalve in a proximal direction. It is appreciated that the valve may alsobe optimized to reduce blood flow in the distal direction. The radialforce of the valve can be tuned by adjusting the braid angle. Tuning theradial force allows the blood flow to be reduced by up to more than 50percent. By way of example, providing a braid angle greater than 130°will significantly reduce blood flow past the valve in the distaldirection, with a braid angle of approximately 150° slowing the bloodflow by 50 to 60 percent. Other braid angles can provide differentreductions in distal blood flow. The reduced distal blood flow can beused in place of a ‘wedge’ technique, in which distal blood flow isreduced for treatment of brain and spinal arteriovenous malformations.Once the blood flow is slowed by the valve, a glue such as acyanoacrylic can be applied at the target site.

There have been described and illustrated herein multiple embodiments ofdevices and methods for reducing or preventing reflux of embolizationagents in a vessel. While particular embodiments of the invention havebeen described, it is not intended that the invention be limitedthereto, as it is intended that the invention be as broad in scope asthe art will allow and that the specification be read likewise. Thuswhile particular deployment means for the protection valve have beendescribed, such as a catheter, a sleeve and control element, a fabricsleeve with a control thread, etc., it will be appreciated that otherdeployment mechanisms such as balloons, absorbable sleeves, orcombinations of elements could be utilized. Likewise, while variousmaterials have been listed for the valve filaments, the valve filter,the catheter, and the deployment means, it will be appreciated thatother materials can be utilized for each of them. Also, while theinvention has been described with respect to particular arteries ofhumans, it will be appreciated that the invention can have applicationto any blood vessel and other vessels, including ducts, of humans andanimals. In particular, the apparatus can also be used in treatments oftumors, such as liver, renal or pancreatic carcinomas. Further, theembodiments have been described with respect to their distal endsbecause their proximal ends can take any of various forms, includingforms well known in the art. By way of example only, the proximal endcan include two handles with one handle connected to the inner(delivery) catheter, and another handle connected to an outer catheteror sleeve or actuation wire or string. Movement of one handle in a firstdirection relative to the other handle can be used to deploy the valve,and where applicable, movement of that handle in an opposite seconddirection can be used to recapture the valve. Depending upon the handlearrangement, valve deployment can occur when the handles are moved awayfrom each other or towards each other. As is well known, the handles canbe arranged to provide for linear movement relative to each other orrotational movement. If desired, the proximal end of the inner cathetercan be provided with hash-marks or other indications at intervals alongthe catheter so that movement of the handles relative to each other canbe visually calibrated and give an indication of the extent to which thevalve is opened. It will therefore be appreciated by those skilled inthe art that yet other modifications could be made to the providedinvention without deviating from its spirit and scope as claimed.

We claim:
 1. An endovascular system for use in a vessel having a vesselwall during an intravascular procedure, comprising: a) an inner catheterhaving a proximal end and a distal end; b) an outer catheter having aproximal end and a distal end; c) a handle system operably coupled tothe proximal ends of the inner and outer catheters, the handle systemincluding a first handle portion and second handle portion movablerelative to the first handle portion, the first handle portion coupledto the inner catheter and a second handle portion coupled to the outercatheter; and d) a microvalve coupled to the distal ends of the innerand outer catheters, the microvalve held in a radially-collapsedundeployed state for advancement within the vessel, and expandable fromthe undeployed state into a radially-expanded deployed state; whereinthe handle system is operable to linearly displace the inner and outercatheters relative to each other to move the microvalve betweenundeployed state and deployed states; and e) a visual indicatorindicating an extent to which the microvalve is opened.
 2. Theendovascular system of claim 1, wherein: the first and second handleportions are linearly displaceable relative to each other.
 3. Theendovascular system of claim 1, wherein: the indicator includescalibrated hash marks.
 4. The endovascular system of claim 1, wherein:the microvalve includes an elastic filamentary structure at leastpartially covered with a filter having a pore size not exceeding 500 μm.5. The endovascular system of claim 4, wherein: the filamentarystructure comprises a braided construct.
 6. The endovascular system ofclaim 1, wherein: the microvalve is dynamically movable within thevessel depending on a local fluid pressure about the microvalve suchthat, when the fluid pressure is higher on a proximal side of themicrovalve than on the distal side of the microvalve, the microvalveassumes a first diameter smaller than a diameter of the vessel such thatblood flow about the valve is permitted, and when the fluid pressure ishigher on a distal side of the microvalve than on the proximal side ofthe microvalve, the microvalve assumes a second diameter relativelylarger than the first diameter and in which the valve is adapted tocontact the vessel wall.
 7. The endovascular system of claim 1, wherein:in the deployed state the microvalve has a radial force of less than 40mN.
 8. The endovascular system of claim 1, wherein: in the deployedstate the microvalve has a radial force of less than 20 mN.
 9. Theendovascular system of claim 1, wherein: in the deployed state themicrovalve has a radial force of approximately 10 mN.
 10. Theendovascular system of claim 1, wherein: in the deployed state themicrovalve has a radial force of approximately 5 mN.
 11. An endovascularsystem for use in a vessel having a vessel wall during an intravascularprocedure, comprising: a) an inner catheter having a proximal end and adistal end; b) an outer catheter having a proximal end and a distal end;c) a handle system operably coupled to the proximal ends of the innerand outer catheters, the handle system including a first handle portionand second handle portion movable relative to the first handle portion,the first handle portion coupled to the inner catheter and the secondhandle portion coupled to the outer catheter; and d) a microvalvecoupled to the distal ends of the inner and outer catheters, themicrovalve constrained in a radially-collapsed closed configuration foradvancement within the vessel, and expandable from the closed state intoa radially-expanded open configuration; wherein linear displacement ofthe first and second handle portions relative to each other moves themicrovalve between the closed configuration and the open configuration;and e) an indicator indicating an extent to which the microvalve isopened.
 12. The endovascular system of claim 11, wherein: the first andsecond handle portions are linearly displaceable relative to each other.13. The endovascular system of claim 11, wherein: the indicator includescalibrated hash marks.
 14. The endovascular system of claim 11, wherein:the microvalve includes an elastic filamentary structure at leastpartially covered with a filter having a pore size not exceeding 500 μm.15. The endovascular system of claim 14, wherein: the filamentarystructure comprises a braided construct.
 16. The endovascular system ofclaim 11, wherein: the microvalve is dynamically movable within thevessel depending on a local fluid pressure about the microvalve suchthat, when the fluid pressure is higher on a proximal side of themicrovalve than on the distal side of the microvalve, the microvalveassumes a first diameter smaller than a diameter of the vessel such thatblood flow about the valve is permitted, and when the fluid pressure ishigher on a distal side of the microvalve than on the proximal side ofthe microvalve, the microvalve assumes a second diameter relativelylarger than the first diameter and in which the microvalve is adapted tocontact the vessel wall.
 17. The endovascular system of claim 11,wherein: in the deployed state the microvalve has a radial force of lessthan 40 mN.
 18. The endovascular system of claim 11, wherein: in thedeployed state the microvalve has a radial force of less than 20 mN. 19.The endovascular system of claim 11, wherein: in the deployed state themicrovalve has a radial force of approximately 10 mN.
 20. Theendovascular system of claim 11, wherein: in the deployed state themicrovalve has a radial force of approximately 5 mN.